Abstract

In this study we explore the antimalarial effects of 3-hydroxypyridin-4-ones (CP compounds), a family of bidentate orally effective iron chelators in experimental animal systems in vivo and in vitro, and examine whether the iron chelator deferoxamine (DF) is active against human infection with P. falciparum. There was direct relation between lipid solubility of the CP compounds, which would facilitate membrane transit, and their in vivo antimalarial action, suggesting direct intracellular iron chelation as the most likely explantation for the antimalarial effect of iron chelators. Results of the double-blind, placebo controlled trial of DF in humans with asymptomatic parasitemia provided unequivocal evidence that this iron-chelating agent has antimalarial activity. Depriving the parasite of a metabolically important source of iron may represent a novel approach to antimalarial drug development. DF is a relatively ineffective intraerythrocytic chelator, and our data indicate that other orally effective iron chelators may have superior antimalarial activity in vivo. A systematic screening of available iron chelating drugs may result in the identification of potentially useful antimalarial compounds.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 07/02/2016 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/1431886